This proposal for a mentored patient-oriented research career development award will provide the candidate with a broad knowledge in the design and conduct of complex clinical oral health trials and the ability to bridge the gap between direct patient assessment, treatment and sampling, and complimentary basic laboratory research. The didactic portion of the training emphasizes courses in clinical research ethics as well as courses in study design, biostatistics, epidemiology, and outcomes assessment. The clinical research component involves an investigation of treatment effects on early onset (rapidly progressive) periodontitis patients and understanding the host response mechanisms involved in tooth debridement in this patient group. In most periodontitis patients, treatment by scaling and root planing results in marked improvement of clinical status. This improvement has traditionally been related to the removal of bacterial substances from the root surfaces. We hypothesize that a portion of the observed improvement results from treatment-induced activation of the host defense mechanisms following scaling and root planing. We will determine whether significant improvement in periodontal health can be demonstrated for untreated teeth in mouths otherwise treated by scaling and root planing and assess the role of antibodies and the mediators released by inflammatory cells in effecting these changes at untreated sites. Future studies will examine the efficacy of other forms of periodontal therapy including surgical flap debridement and dental implant rehabilitation. Forty adults having rapidly progressive periodontitis (RPP) will be randomized into treatment and no treatment groups. The treatment group will have all teeth scaled and root planed except for three teeth clustered in a single experimental quadrant. The teeth in the no treatment group will not be treated until the termination of the study, twelve months later. The outcome for treated and untreated teeth will be assessed by measurement of clinical parameters including pocket depth and attachment level, changes in alveolar bone density and height by digital subtraction radiography, changes in serum antibody titers for suspected periodontal pathogens, and expression of inflammatory mediators (IL-1beta and PGE2) in the gingival crevicular fluid. Based on data from a completed pilot study, we estimate that as much as one-half of the improvement observed following scaling and root planing may be due to factors other than just the removal of plaque, calculus, and irritants. This project will enhance our understanding of the effects of root debridement on host defense systems and help to develop more effective treatment options for this complex inflammatory disease.